IdA stringlengths 6 21 | IdB stringlengths 6 21 | labels int64 0 2 | mechanism stringclasses 40 values | effect stringclasses 10 values | score float64 0.1 0.99 ⌀ | sentence stringlengths 10 1.63k ⌀ | signor_id stringlengths 12 14 |
|---|---|---|---|---|---|---|---|
Q12933 | P62714 | 0 | dephosphorylation | down-regulates activity | 0.2 | We show that the Thr117 residue in TRAF2 is phosphorylated following TNFalpha stimulation. This phosphorylation process is modulated by PP2A and is required for TRAF2 functional activity. | SIGNOR-248597 |
Q99626 | Q07654 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.391 | The transcription of human TFF3 reporter genes was significantly up-regulated by the transient overexpression of CDX2 in COS-7 cells and AGS gastric cells. | SIGNOR-253967 |
O00213 | Q63HK5 | 1 | relocalization | up-regulates activity | 0.366 | We carried out yeast two-hybrid studies with a PTB domain of FE65, focusing on those genes that might be involved in nuclear signaling, and identified and validated Teashirt proteins as FE65 interacting proteins in neurons. Using reporter systems, we observed that FE65 could simultaneously recruit SET, a component of the inhibitor of acetyl transferase, and Teashirt, which in turn recruited histone deacetylases, to produce a powerful gene-silencing complex. | SIGNOR-264813 |
Q13541 | P49674 | 0 | phosphorylation | down-regulates | 0.2 | Mechanistic investigations showed that ck1_ interacted with and phosphorylated 4e-bp1 at two novel sites t41 and t50, which were essential for 4e-bp1 inactivation along with increased mrna translation and cell proliferation. | SIGNOR-203240 |
Q9BXH1 | P10415 | 2 | binding | down-regulates activity | 0.663 | Only bimbh3 and bbc3 had comparable strong affinitiesfor all the prosurvival proteins. The members that promote cell survival, including mammalian bcl-2, bcl-xl,bcl-w, mcl-1, and a1. | SIGNOR-133808 |
P49841 | Q13950 | 1 | phosphorylation | down-regulates activity | 0.301 | Collectively, these data demonstrate that the kinase activity of GSK-3beta suppresses the Runx2 transcriptional activity.|In vitro kinase assay confirmed that the Runx2 phosphorylation by GSK-3\u03b2 was reduced by the S369-S373-S377 mutation ( xref ). | SIGNOR-279051 |
Q9UHI6 | P41162 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.739 | ETV3 target genes including etv3, ddx20, and dusp6 provide negative feedback regulation of ETV3 production and activity. Negative feedback along with constitutive instability may serve to tightly regulate ETV3 abundance. Our date suggest that phosphorylation by ERK2 relieves repression by ETV3, allowing activation of cell cycle control genes including myc, components of the NF-κB pathway, and genes required form RNA processing and translation. | SIGNOR-262779 |
P68400 | P13349 | 1 | phosphorylation | up-regulates activity | 0.307 | Here, we report that Myf-5 protein constitutes a substrate for phosphorylation in vitro by protein kinase CK2. We identified two potential phosphorylation sites at serine49 and serine133, both of which seem to be necessary for Myf-5 activity. | SIGNOR-250922 |
O95972 | Q13873 | 2 | binding | up-regulates | 0.536 | Here we have performed a detailed in situ hybridization analysis of the spatial and temporal expression patterns of the bmp ligands (bmp-2, -3, -3b, -4, -6, -7, -15), receptors (bmpr-ia, -ib, -ii), and bmp antagonist, follistatin, in rat ovaries over the normal estrous cycle. | SIGNOR-144098 |
Q9UNH5 | Q7Z569 | 0 | polyubiquitination | up-regulates activity | 0.337 | Brap2 promotes Lys-63 linked ubiquitination of HsCdc14A. Collectively, these results support the idea that Brap2 facilitates Lys-63 linked ubiquitin modification of HsCdc14A, which may not be targeted for degradation, but mainly for protein–protein interactions or other regulatory functions. | SIGNOR-271777 |
Q92973 | P49790 | 1 | relocalization | up-regulates activity | 0.499 | TNPO1 only mediates the nuclear import of a subset of proteins.|Among TNPO1 cargos, the most extensively characterized is the RNA binding protein heterogeneous nuclear ribonucleoprotein 1 (hnRNPA1) (27), which functions in several processes including mRNA biogenesis and promotion of transcription factor activity (28–30). NPC protein NUP153 is also a target for TNPO1-mediated nuclear import | SIGNOR-262100 |
Q8NES3 | O00548 | 2 | binding | up-regulates | 0.447 | The modification of notch by fringe would influence binding between the notch receptor and its ligand. It was reported previously that mfng and lfng inhibited notch1-mediated signaling triggered by jagged1 and enhanced that triggered by delta1, and either jagged1- or delta1-triggered notch2 signaling was enhanced by lfng | SIGNOR-107699 |
Q9ULV8 | Q14155 | 2 | binding | down-regulates | 0.2 | Here, we show that activation of cdc42 protects the egf receptor from the negative regulatory activity of the c-cbl ubiquitin ligase. Activated cdc42 binds to p85cool-1 (for cloned-out-of-library)/beta-pix (for pak-interactive exchange factor), a protein that directly associates with c-cbl. This inhibits the binding of cbl by the egf receptor and thus prevents cbl from catalyzing receptor ubiquitination | SIGNOR-118135 |
Q96L73 | P10163 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.342 | We here demonstrate that NSD1 could bind to the promoter regions of PRB4 and activate promoter activity by reducing the binding of H3K27me2 and increasing the binding of H3K36me2 on PRB4 promoter. | SIGNOR-268459 |
P63096 | Q9Y5N1 | 2 | binding | up-regulates activity | 0.437 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-256689 |
Q01094 | P32780 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.434 | TFIIH-mediated phosphorylation of E2F-1 plays a role in triggering E2F-1 degradation during S phase. E2F-1 activation domain interacts with a kinase activity which phosphorylates two sites, Ser403 and Thr433, within the activation domain. We demonstrate that TFIIH is responsible for the E2F-1 phosphorylation observed in cell extracts and that endogenous E2F-1 interacts in vivo with p62, a component of TFIIH, during S phase. | SIGNOR-251260 |
P04049 | P53041 | 0 | dephosphorylation | down-regulates activity | 0.462 | Protein phosphatase 5 (PP5) was identified as an inactivator that associates with Raf-1 on growth factor stimulation and selectively dephosphorylates an essential activating site, Ser 338. The PP5-mediated dephosphorylation of Ser 338 inhibited Raf-1 activity and downstream signalling to MEK | SIGNOR-248537 |
P29320 | P10275 | 1 | phosphorylation | up-regulates activity | 0.273 | These data suggest that Etk may be able to phosphorylate AR at Y534 and Y551/552, and the interaction between the Etk SH2 domain and phosphorylated ARY551/552 may promote their association.|This is supported by our observations that the association between Etk and AR is increased after castration and Etk induces tyrosine phosphorylation of AR, leading an increase in AR stability and transcriptional activity under androgen depleted conditions. | SIGNOR-279371 |
P06493 | Q14739 | 1 | phosphorylation | down-regulates | 0.396 | The binding of the nk fragment to chromatin pretreated with an s-phase extract was suppressed by incubation with an m-phase extract. Enzyme inhibitor experiments revealed that multiple kinases participate in the suppression. One of these kinases was shown to be cdc2 experiments involving a mutant nk fragment showed that the phosphorylation of serine 71 by cdc2 kinase is responsible for the suppression. | SIGNOR-121335 |
Q13415 | P06493 | 0 | phosphorylation | up-regulates | 0.637 | Horc1p contains three (s/t)px(k/r) consensus sites for cdk phosphorylation (ser258, ser273, and thr375). These data combined strongly suggest that skp2 promotes horc1p turnover and that the n-terminal domain of horc1p, containing most of the phosphorylation sites and overlapping with one of the skp2-interacting domains, is a regulatory element for horc1p stability. | SIGNOR-116329 |
Q6T4R5 | Q9Y2A7 | 2 | binding | up-regulates activity | 0.2 | We show that the WHD of NHS interacts with the Abi family of proteins, HSPC300, Nap1 and Sra1, and is important for the localization of NHS to the leading edge. | SIGNOR-253576 |
Q14344 | P29371 | 2 | binding | up-regulates activity | 0.283 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-257438 |
O75061 | P11142 | 1 | relocalization | up-regulates activity | 0.883 | Hsc70, recruited by the J-domain protein auxilin, mediates clathrin uncoating and release of a free vesicle, primed to fuse with a target membrane. | SIGNOR-260719 |
P30307 | Q13535 | 0 | phosphorylation | up-regulates activity | 0.643 | We also found that activated ATR phosphorylates CDC25C (Cell Division Cycle 25C) at serine 216, which in turn inactivates the cyclin B1/Cyclin-Dependent Kinase 1(CDK1) complex and induces G2-phase arrest. | SIGNOR-279008 |
Q12986 | Q96ST3 | 2 | binding | up-regulates activity | 0.373 | we investigated the mechanism of NFX1-91 repression of the hTERT promoter and demonstrated that NFX1-91 interacts with the corepressor mSin3A/HDAC to maintain the deacetylated status at the hTERT promoter, thus providing a mechanism by which NFX1-91 represses hTERT expression. | SIGNOR-226360 |
P05067 | Q86TM6 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.339 | Thus, HRD1 ubiquitinates and degrades denaturated APP as well as unfolded proteins, suggesting that HRD1 affects APP-A\u03b2 dynamics in the brains of AD patients. | SIGNOR-278616 |
P21860 | O00329 | 2 | binding | up-regulates | 0.416 | Pi3k is the sole binding partner to six tyrosines of erbb3 and one in erbb4. | SIGNOR-146867 |
P28300 | O95967 | 2 | binding | up-regulates activity | 0.561 | Fibulin-4 directly binds LOX, and this interaction enhances fibulin-4 binding to tropoelastin, thus forming a ternary complex that may be critical for elastin cross-linking. | SIGNOR-252135 |
P16070 | Q9ULU4 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Our quantitative ChIP experiments confirmed that ZMYND8 and JARID1D were co-localized at Slug, CD44, VEGFA, and EGFR genes (Figures 4F–4I). Our ChIP results also showed that ZMYND8 repressed and occupied other JARID1D target genes, such as the matrix metalloproteinase 1 (MMP1) and MMP3, that we previously reported | SIGNOR-262039 |
Q8WV44 | Q8N884 | 1 | ubiquitination | up-regulates activity | 0.2 | Our finding that RINCK positively regulates cGAS activation by mediating the monoubiquitination of cGAS uncovers the function of RINCK in cGAS mediated innate immunity.|Together, these data suggest that RINCK mediates cGAS monoubiquitination. | SIGNOR-278794 |
P20807 | Q15078 | 1 | cleavage | up-regulates activity | 0.261 | Calpains also modulate the activity of CDK5. Physiologically, CDK 5 is activated by p35 and its cleaved product p25. The latter has a longer half life than p35 and therefore it is a more potent activator of CDK5. The cleavage of p35 to p25 is mediated by calpain | SIGNOR-251604 |
P23443 | P04792 | 1 | phosphorylation | down-regulates | 0.309 | Ser-15, ser-78, and ser-82 in hsp27 (ser-15 and ser-86 in hsp25) are part of the rxxs motif, a known recognition site for p70rsk. | SIGNOR-186959 |
P01178 | Q92824 | 0 | cleavage | down-regulates quantity | 0.248 | Oxytocin-extended form is further cleaved by enzymatic activity to yield the nine-amino-acid active peptide, OT. The proteolysis may involve several pro-hormone convertases, convertase 2 (PC2) (20p11-1-11.2) and convertase 5 (PC5) (9q21.3) (Gabreels et al 1998). Both enzymes are found in OT neurosecretory vesicles and are a part of a family of subtilisen/kexinlike convertases (Seidah et al 1994). It is a product of the OT gene located at human gene locus 20p13 (Rao et al 1992). The processing cascade results in the production of neurophysin I and OT extended form (OT-X), which is OT with a C-terminal, three-amino-acid extension. | SIGNOR-270327 |
P29372 | P61077 | 2 | binding | up-regulates activity | 0.2 | Here we report that MID1 catalyzes the in vitro ubiquitination of the catalytic subunit of PP2A (PP2Ac) in the absence of alpha4. In the presence of alpha4, the level of PP2Ac ubiquitination is reduced.The high molecular weight smear pattern was not as obvious, suggesting that domains within the C-terminal half of MID1 may contribute to the polyubiquitination of PP2Ac. We observed that PP2Ac was ubiquitinated in the presence of UbcH5a-c and UbcH6, similar to results obtained with MID1-catalyzed ubiquitination of alpha4 (Figure 2E) | SIGNOR-271928 |
P24941 | Q8WVD3 | 1 | phosphorylation | up-regulates activity | 0.2 | Altogether, our results suggest RNF138 is phosphorylated at position T27 in a CDK1- and CDK2-dependent manner.Altogether, our results suggest RNF138 is phosphorylated at position T27 in a CDK1- and CDK2-dependent manner. | SIGNOR-277831 |
O95835 | P17612 | 0 | phosphorylation | up-regulates | 0.2 | Here, we show that cyclic amp (camp)-dependent protein kinase (pka) phosphorylates lats and thereby enhances its activity sufficiently to phosphorylate yap on ser381. | SIGNOR-236991 |
Q8N699 | P01106 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.298 | MT-MC1 is a widely expressed nuclear protein whose overexpression, unlike that of c-Myc targets reported previously, recapitulates multiple c-Myc phenotypes. These include promotion of apoptosis, alteration of morphology, enhancement of anchorage-independent growth, tumorigenic conversion, promotion of genomic instability, and inhibition of hematopoietic differentiation. The MT-MC1 promoter is a direct c-Myc target; it contains two consensus E-box elements, both of which bind c-Myc. | SIGNOR-261736 |
P19086 | P21453 | 2 | binding | up-regulates activity | 0.385 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-257108 |
Q15831 | P27448 | 1 | phosphorylation | up-regulates activity | 0.315 | Regulation of the wnt signalling component par1a by the peutz-jeghers syndrome kinase lkb1. Lkb1 is a master kinase that activates 13 kinases of the ampk subfamily, including mark/par-1. Mark3 is activated by phosphorylation on thr-211. | SIGNOR-104059 |
P49768 | P17252 | 0 | phosphorylation | up-regulates activity | 0.264 | A phosphorylation site at serine residue 346 was identified that is selectively phosphorylated by PKC but not by PKA. This site is localized within a recognition motif for caspases, and phosphorylation strongly inhibits proteolytic processing of PS1 by caspase activity during apoptosis. | SIGNOR-249236 |
P04085 | P16234 | 2 | binding | up-regulates | 0.773 | Platelet-derived growth factors (pdgf) constitute a family of four gene products (pdgf-a-d) acting by means of two receptor tyrosine kinases, pdgfr alpha and beta. Three of the ligands (pdgf-a, -b, and -c) bind to pdgfr alpha with high affinity. | SIGNOR-114268 |
Q4G0P3 | P43694 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | HYDIN promotes expression of Gata4 in cardiomyocyte differentiation. HYDIN functions as a positive regulator of human cardiomyocyte differentiation and promotes expression of cardiac contractile genes in hESC cells. This is mediated through GATA4, a critical transcription factor in heart development. Cardiac-specific Hydin knockdown in vivo leads to Gata4 downregulation and enhanced atrial septal defect (ASD) risk in mice. GATA4 is a fundamental TF in embryonic heart development and cardiac differentiation, and reduction in GATA4 function results in a diverse range of CHDs | SIGNOR-265479 |
O75084 | O14640 | 2 | binding | up-regulates | 0.661 | In non-canonical Wnt signalling, Wnt proteins bind Fzd and glypican-4, to activate Dsh at the cell membrane, leading to activation of Rho and JNK | SIGNOR-255893 |
Q13148 | P49841 | 1 | post transcriptional regulation | down-regulates quantity by repression | 0.267 | Importantly, we found that TDP-43 protein could interact with GSK3β mRNA and regulate the level of GSK3β protein translation. Taken together, our findings suggest that TDP-43 may activate the Wnt/β-catenin pathway by targeting the inhibition of GSK3β protein translation|TDP-43 activates Wnt/β-catenin pathway probably by inhibiting the GSK3β protein translation. A. Interaction between TDP-43 protein and GSK3β mRNA was analyzed using RIP assay. | SIGNOR-262113 |
P33151 | P12931 | 0 | phosphorylation | down-regulates activity | 0.567 | cadherins also act to prevent epithelial cell motilityCadherin-cytoskeletal interactions occur through a number of adaptor proteins that interact with the C-terminal portion of the cadherin cytoplasmic tail, including the _-, _-, and _-catenin (6, 10). Additionally, VE-cadherin stability at the plasma membrane may be regulated by the binding of p120-catenin to the juxtamembrane region of the cytoplasmic tailWe show here that tyrosine phosphorylation of the adherens junction protein VE-cadherin at two critical tyrosines, Tyr-658 and Tyr-731, via tyrosine kinase activation or phosphatase inactivation was sufficient to prevent the binding of p120- and beta-catenin, respectively, to the cytoplasmic tail of VE-cadherinVE-cadherin becomes phosphorylated on Tyr-658 and/or Tyr-731 in response to Src kinase activity. | SIGNOR-246462 |
P04049 | P17252 | 0 | phosphorylation | down-regulates | 0.558 | Pka can inhibit raf-1 function directly via phosphorylation of the raf-1 kinase domain | SIGNOR-34761 |
P52789 | P12931 | 0 | phosphorylation | up-regulates activity | 0.362 | Here we find that c-Src can interact with and phosphorylate hexokinases HK1 and HK2, the rate limiting enzymes in glycolysis.|Moreover, c-Src could efficiently stimulate the catalytic activities of HK1 and HK2, but failed to stimulate their corresponding mutants (XREF_FIG and XREF_SUPPLEMENTARY). | SIGNOR-278499 |
Q9Y5I2 | Q9UN71 | 2 | binding | up-regulates activity | 0.2 | The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. They also form oligomers with Pcdh-gamma proteins at the same membrane sites. | SIGNOR-265701 |
Q96EB6 | P06493 | 0 | phosphorylation | up-regulates | 0.528 | We identified cyclinb/cdk1 as a cell cycle-dependent kinase that forms a complex with and phosphorylates sirt1. Mutation of two residues phosphorylated by cyclin b/cdk1 (threonine 530 and serine 540) disturbs normal cell cycle progression and fails to rescue proliferation defects in sirt1-deficient cells | SIGNOR-182863 |
Q9NRC8 | Q6NXT2 | 1 | deacetylation | up-regulates activity | 0.2 | Besides confirming the previously reported histone H3K18 deacylation activity, our results revealed that SIRT7 has an astonishingly high activity to catalyze deacylation of H3K36 and is also catalytically active to deacylate H3K37. | SIGNOR-275879 |
O14713 | P18564 | 2 | binding | down-regulates activity | 0.287 | Integrins also bind to many PTBdomain-containing proteins (Calderwood et al., 2003) – including Dok1 and integrincytoplasmic-domain-associated protein 1 (ICAP1) – and these can compete with talin for binding to integrin and so can impair activation | SIGNOR-257662 |
P78352 | Q12840 | 2 | binding | up-regulates activity | 0.313 | Postsynaptic density protein 95 (PSD-95) is transported by KIF5 to dendritic regions | SIGNOR-264065 |
Q15797 | Q13950 | 2 | binding | up-regulates | 0.538 | Smad1 interacts with runx2 on the promoter of target genes and controls osteoblast gene expression and differentiation | SIGNOR-195642 |
Q96M98 | P0DMV8 | 2 | binding | up-regulates quantity by stabilization | 0.2 | Our in vitro data suggest that CHIP competes with Hsp70 in binding to Parkin, probably via suppression of the ATPase activity of Hsc/Hsp70 (Figure 4E).In fact, it acts as an inhibitory factor that suppresses the ubiquitination of Pael-R mediated by Parkin in vitro, and Hsp70 enhances the efficiency of folding of overexpressed Pael-R in vivo. | SIGNOR-272890 |
Q9GZQ4 | P19086 | 2 | binding | up-regulates activity | 0.268 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-257126 |
P15514 | P12931 | 0 | cleavage | up-regulates | 0.345 | Ep2 can also promote the transactivation of epidermal growth factor receptor (egfr) expressed in colon cancer cells through src, which activates the proteolytic release of the egfr ligands amphiregulin (ar) and transforming growth factor-alfa (tgfalfa)125, thereby stimulating the egfr- network. | SIGNOR-236537 |
A0AVK6 | O14757 | 0 | phosphorylation | down-regulates activity | 0.315 | Chk1 inhibits the transcriptional repressor function of E2F7 and E2F8 to promote cell cycle progression and prevent apoptosis.|Here, we demonstrate that Chk1 phosphorylates both E2F7 and E2F8 in response to DNA damage. | SIGNOR-279693 |
P04637 | P67775 | 0 | dephosphorylation | down-regulates activity | 0.59 | Phosphorylation of p53 at serine 37 is important for transcriptional activity and regulation in response to DNA damage| Furthermore, in vitro phosphatase assays show that PP2A dephosphorylates p53 at S37. | SIGNOR-248619 |
Q6N021 | P22607 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.25 | FGFR3∆7-9, but not wild-type FGFR3, directly interacts with TET2 and phosphorylates TET2 at Y1902 site, leading to the ubiquitination and proteasome-mediated degradation of TET2. | SIGNOR-277535 |
P17252 | Q8IZQ8 | 1 | phosphorylation | down-regulates activity | 0.2 | PKCalpha directly promoted the basal phosphorylation of endogenous myocardin at serine and threonine residues. | SIGNOR-279099 |
Q14164 | Q9UNN5 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.283 | Upon virus infection, the kinase IKKɛ directly phosphorylates FAF1 at Ser556 and triggers FAF1 de-aggregation. Moreover, Ser556 phosphorylation promotes FAF1 lysosomal degradation, consequently relieving FAF1-dependent suppression of MAVS. | SIGNOR-277618 |
Q96AP0 | P27694 | 2 | binding | down-regulates activity | 0.2 | The current model for how telomeres repress ATR signaling proposes that POT1/TPP1 prevents the binding of RPA to the single-stranded telomeric DNA | SIGNOR-263328 |
P24941 | P29374 | 1 | phosphorylation | down-regulates | 0.426 | In the present study we identified rbp1 as a novel cdk substrate. Rbp1 is phosphorylated by cdk2 on serines 864 and 1007, which are n- and c-terminal to the lxcxe motif, respectively. Cdk2-mediated phosphorylation of rbp1 or prb destabilizes their interaction in vitro, with concurrent phosphorylation of both proteins leading to their dissociation | SIGNOR-170455 |
Q9UHD2 | P42858 | 1 | phosphorylation | up-regulates activity | 0.289 | Herein, we report the discovery and validation of a kinase, TANK-binding kinase 1 (TBK1), that efficiently phosphorylates full-length and N-terminal HTT fragments in vitro (at S13/S16), in cells (at S13) and in vivo. TBK1 expression in HD models (cells, primary neurons, and Caenorhabditis elegans) increases mutant HTT exon 1 phosphorylation and reduces its aggregation and cytotoxicity. | SIGNOR-270350 |
P00797 | P19544 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.421 | Here, we show that a splice variant of the Wilms' tumor protein lacking three amino acids WT1(-KTS) suppresses renin gene transcription | SIGNOR-252296 |
Q9UJQ4 | Q96SW2 | 2 | binding | down-regulates quantity by destabilization | 0.2 | Thalidomide-induced teratogenicity is dependent on its binding to cereblon (CRBN), the substrate receptor of the Cul4A-DDB1-CRBN-RBX1 E3 ubiquitin ligase complex. Thalidomide binding to CRBN elicits subsequent ubiquitination and proteasomal degradation of CRBN neosubstrates including SALL4, a transcription factor of which polymorphisms phenocopy thalidomide-induced limb defects in humans. | SIGNOR-272208 |
P17706 | P51692 | 1 | dephosphorylation | down-regulates activity | 0.733 | In the previous study, we demonstrated that the nuclear isoform of T-cell protein-tyrosine phosphatase (TC-PTP) dephosphorylated and deactivated signal transducer and activator of transcription 5a (STAT5a) and STAT5b, thereby negatively regulating prolactin (PRL)-mediated signaling pathway. | SIGNOR-277126 |
Q96EB6 | Q9Y5P2 | 2 | binding | up-regulates activity | 0.2 | Here, we show that the previously undescribed CSAG2 protein is a direct activator of SIRT1. Biochemical studies revealed that CSAG2 directly binds to and stimulates SIRT1 activity toward multiple substrates. Importantly, CSAG2 enhances SIRT1‐mediated deacetylation of p53, inhibits p53 transcriptional activity, and improves cell survival in response to genotoxic stress. | SIGNOR-261670 |
P35558 | Q8IXJ6 | 0 | deacetylation | up-regulates quantity by stabilization | 0.426 | Conversely, SIRT2 deacetylates and stabilizes PEPCK1.|Furthermore, coexpression of P300 increased acetylation levels of wild-type PEPCK1, but not PEPCK13K/R, indicating that P300 acts on these lysine residues of PEPCK1 | SIGNOR-267599 |
Q9UJD0 | Q01668 | 2 | binding | up-regulates activity | 0.2 | Here, we report an interaction of the C2B domain of RIM2α and RIM3γ with the C-terminus of the pore-forming α-subunit of CaV1.3 channels (CaV1.3α1), which mediate stimulus-secretion coupling at the ribbon synapses of cochlear inner hair cells (IHCs). In conclusion, we propose that RIM2α and RIM3γ directly interact with the C-terminus of the pore-forming subunit of CaV1.3 Ca2+ channels and positively regulate their plasma membrane expression in HEK293 cells. | SIGNOR-264357 |
O60260 | P19174 | 1 | ubiquitination | down-regulates quantity | 0.2 | In order to address the functional role of parkin ubiquitination of PLCgamma1, we investigated PLC activity in human neuroblastoma SH-SY5Y cell lines stably transfected with either WT, or mutant R42P or G328E parkin.|WT parkin expression significantly reduced the levels of PLCgamma1 in human neuroblastoma. | SIGNOR-278592 |
P10275 | P07900 | 2 | binding | up-regulates activity | 0.763 | The unliganded AR resides predominately in the cytoplasm as a heteromeric complex with hsp90 and other chaperone proteins. These chaperone proteins maintain AR in a form that is receptive to ligand binding. Regulation of gene expression by androgen-activated AR occurs through receptor nuclear translocation, dimerization, and binding to androgen response elements (AREs) in the DNA of target genes. | SIGNOR-251536 |
P10636 | P17655 | 0 | cleavage | down-regulates activity | 0.433 | Besides tau phosphorylation, calpain activation might play a role in tau-mediated neurodegeneration by inducing tau cleavage. In vitro studies have shown that both fetal and adult tau isoforms are rapidly proteolyzed by calpains | SIGNOR-251611 |
Q13315 | Q13541 | 1 | phosphorylation | down-regulates | 0.512 | Here we report that atm... phosphorylates 4e-bp1 at ser 111cells lacking atm kinase activity exhibit a significant decrease in the insulin-induced dissociation of 4e-bp1 from eif-4e. | SIGNOR-85619 |
P49137 | Q01860 | 1 | phosphorylation | up-regulates activity | 0.2 | MK2 mediated OCT4 transcriptional activation is a novel mechanism for activating the MYC oncogene in progressive disease neuroblastoma that provides a therapeutic target.|OCT4 phosphorylation at the S111 residue by MK2 was upstream of MYC transcriptional activation. | SIGNOR-279542 |
Q13618 | Q13829 | 2 | binding | up-regulates activity | 0.461 | BACURDs form ubiquitin ligase complexes, which selectively ubiquitinate RhoA, with Cul3. Our studies reveal a previously unknown mechanism for controlling RhoA degradation and regulating RhoA function in various biological contexts, which involves a Cul3/BACURD ubiquitin ligase complex. | SIGNOR-264232 |
P51692 | O60674 | 0 | phosphorylation | up-regulates | 0.865 | Jak2 kinase induces tyrosine phosphorylation, dimerization, nuclear translocation, and dna binding of a concomitantly expressed stat5 protein | SIGNOR-56894 |
P02647 | O95477 | 2 | binding | up-regulates quantity by stabilization | 0.79 | ApoA-I stabilization of ABCA1 is mediated by reduced PEST sequence phosphorylation, which in turn leads to decreased calpain proteolysis of ABCA1. | SIGNOR-252101 |
Q9Y490 | Q00535 | 0 | phosphorylation | up-regulates | 0.458 | Cdk5 phosphorylated talin head at ser 425, inhibiting its binding to smurf1, thus preventing talin head ubiquitylation and degradation. | SIGNOR-185210 |
P17252 | P35568 | 1 | phosphorylation | down-regulates activity | 0.386 | We show that pkcalpha is likely to be directly involved in ser24 phosphorylation...These observations are entirely consistent with a recent independent study demonstrating that the IRS1-S24D mutant shows impaired insulin-stimulated IR-IRS-1 interactions, tyrosine phosphorylation of IRS-1, recruitment/activation of PI 3-Kinase, and insulin-stimulated Glut4 translocation | SIGNOR-145398 |
P17252 | P10636-2 | 1 | phosphorylation | down-regulates activity | 0.265 | We have studied the relationship between the phosphorylation oftau by several kinases (MARK, PKA, MAPK, GSK3) and its assembly into PHFs. By contrast, MARK and PKA phosphorylate several sites within the repeats (notably theKXGS motifs including Ser262, Ser324, and Ser356, plus Ser320); in addition PKA phosphorylates somesites in the flanking domains, notably Ser214. This type of phosphorylation strongly reduces tau’s affinityfor microtubules, and at the same time inhibits tau’s assembly into PHFs. | SIGNOR-275441 |
Q09472 | P20962 | 2 | binding | up-regulates activity | 0.322 | Macromolecular translocation inhibitor II (MTI-II), which was first identified as an in vitro inhibitor of binding between the highly purified glucocorticoid receptor (GR) and isolated nuclei, is an 11.5-kDa Zn2+-binding protein that is also known as ZnBP or parathymosin. MTI-II Enhances GR-dependent Transcription through Its Acidic Domain. MTI-II Enhances GR-dependent Transcription in Cooperation with SRC-1 and p300 in Vivo. CBP and p300 Coprecipitate with MTI-II in a Glucocorticoid Hormone-dependent Manner. Immunoprecipitation analysis showed that in the presence of glucocorticoid hormone, p300 and CREB-binding protein are coprecipitated with MTI-II. Furthermore, the knockdown of endogenous MTI-II by RNAi reduces the transcriptional activity of GR in cells. | SIGNOR-268461 |
P05556 | Q9UN75 | 2 | binding | up-regulates activity | 0.2 | The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. | SIGNOR-265673 |
P52797 | P29320 | 2 | binding | up-regulates | 0.804 | The activation of eph receptors by their ligands, which are membrane-anchored molecules, involves a cell-cell recognition event that often causes cell repulsion. transmembrane ligands for eph receptors also exhibit properties of signal transducing molecules, suggesting that bidirectional signaling occurs when receptor-expressing cells contact ligand-expressing cells. | SIGNOR-52312 |
Q15173 | P42574 | 1 | dephosphorylation | up-regulates | 0.2 | Dephosphorylation of caspase-3 at ser150 site by pp2a increased caspase-3 activity,which was essential to trigger apoptosis in neutrophils. | SIGNOR-131435 |
P16591 | P52565 | 1 | phosphorylation | down-regulates activity | 0.2 | Fer interferes with binding of RhoGDI\u03b1 and Rac. (A) GST-RhoGDI\u03b1 was pre-incubated with Rac, after which GST-Fer (G-Fer) or GST (G) was added and GST fusion proteins were pulled down with glutathione agarose, followed by kinase reactions. (B) GST-RhoGDI\u03b1 was pre-incubated with GST-Fer or GST in kinase buffer, after which Rac was added and RhoGDI\u03b1 was immunoprecipitated. 50 pmol of RhoGDI\u03b1 and Rac1, with 25 pmol of GST and GST-Fer were used.|These results identify tyrosine phosphorylation of RhoGDIalpha by Fer as a mechanism to regulate binding of RhoGDIalpha to Rac. | SIGNOR-279042 |
P27361 | Q969V6 | 1 | phosphorylation | down-regulates | 0.2 | Serum induces rhoa-dependent translocation of mkl1 from the cytoplasm to the nucleus and also causes a rapid increase in mkl1 phosphorylation. Serum-induced phosphorylation of the serum response factor coactivator mkl1 by the extracellular signal-regulated kinase 1/2 pathway inhibits its nuclear localization. | SIGNOR-195157 |
P63000 | Q9P227 | 0 | gtpase-activating protein | down-regulates activity | 0.43 | We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2). | SIGNOR-260480 |
P36402 | Q13015 | 2 | binding | up-regulates activity | 0.463 | Here, we show that AF1q specifically binds to T-cell-factor-7 (TCF7) in the Wnt signaling pathway and results in transcriptional activation of CD44 as well as multiple downstream targets of the TCF7/LEF1. Super-shift and electrophoretic mobility shift assay (EMSA) further confirmed that AF1q directly interacted with TCF7 and enhanced the binding affinity of the complex | SIGNOR-259108 |
P06239 | Q9UHD2 | 1 | phosphorylation | down-regulates activity | 0.2 | The Src family kinases (SFKs) Lck, Hck, and Fgr directly phosphorylate TBK1 at Tyr354/394, to prevent TBK1 dimerization and activation. | SIGNOR-276724 |
P04628 | O75197 | 2 | binding | up-regulates activity | 0.788 | Ligands such as wnt1, wnt3a, and wnt8 couple the seventransmembrane domain receptor frizzled (fzd) and the single-membrane-spanning low-density receptor-related protein 5/6 (lrp5/6) to activate wnt?Beta-catenin signaling. | SIGNOR-169645 |
P24588 | Q9UIJ5 | 0 | palmitoylation | up-regulates activity | 0.331 | Here, we report that the recycling endosome-resident palmitoyl acyltransferase DHHC2 interacts with and palmitoylates AKAP79/150 to regulate these plasticity signaling mechanisms | SIGNOR-261289 |
Q9Y463 | P28482 | 0 | phosphorylation | up-regulates activity | 0.369 | S421 resides within a Ser-Pro phosphoacceptor motif that is typical for ERK1/2 and recombinant ERK2 phosphorylated DYRK1B at S421 in vitro. | SIGNOR-276937 |
Q03164 | P17947 | 1 | methylation | up-regulates quantity by expression | 0.441 | Furthermore, we show that both MLL and AML1/CBFβ are required for maintaining the H3K4-me3 mark at the PU.1 upstream regulatory element (URE) and promoter region, and for full PU.1 gene expression. | SIGNOR-255874 |
Q92793 | P10243 | 2 | binding | up-regulates activity | 0.481 | CBP co-operates functionally with A-Myb | SIGNOR-240984 |
Q9BRR9 | P63000 | 1 | gtpase-activating protein | down-regulates activity | 0.606 | We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2). | SIGNOR-260464 |
Q9NRD5 | P17252 | 2 | binding | up-regulates activity | 0.802 | We show that protein interacting with C-kinase 1 (PICK1) recruits activated protein kinase Cα (PKCα) to MycUNC5A at the plasma membrane, stimulating its endocytosis. We identify two PKCα phosphorylation sites at serines 408 and 587, as well as dileucine internalization motifs, which are required for this endocytosis. | SIGNOR-268178 |
O75367 | O43791 | 2 | binding | up-regulates activity | 0.2 | Here, we describe an E3 ubiquitin ligase consisting of SPOP and CULLIN3 that is able to ubiquitinate the PcG protein BMI1 and the variant histone MACROH2A1. BMI1 and MACROH2A1 interact with and are ubiquitinated by the CULLIN3 and SPOP ligase complex. | SIGNOR-272657 |
Q13188 | Q9NS23 | 2 | binding | up-regulates | 0.697 | Mst1/2 is also activated by binding to Ras association domain family (RASSF) proteins, possibly owing to alteration of Mst1/2 subcellular localization. | SIGNOR-175790 |
P41145 | P51608 | 0 | post transcriptional regulation | up-regulates quantity by expression | 0.272 | MeCP2 binds to the promoter region of six target genes. ChIP with anti-MeCP2 antibody shows that MeCP2 binds to the promoter regions of activated targets Sst, Oprk1, Gamt, and Gprin1, and repressed targets Mef2c and A2bp1. | SIGNOR-264677 |
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